The Role of Viruses in the Pathogenesis of Immune-Mediated Gastro-Intestinal Diseases.

Immune-mediated gastrointestinal (GI) diseases, including achalasia, celiac disease, and inflammatory bowel diseases, pose significant challenges in diagnosis and management due to their complex etiology and diverse clinical manifestations. While genetic predispositions and environmental factors have been extensively studied in the context of these conditions, the role of viral infections and virome dysbiosis remains a subject of growing interest. This review aims to elucidate the involvement of viral infections in the pathogenesis of immune-mediated GI diseases, focusing on achalasia and celiac disease, as well as the virome dysbiosis in IBD. Recent evidence suggests that viral pathogens, ranging from common respiratory viruses to enteroviruses and herpesviruses, may trigger or exacerbate achalasia and celiac disease by disrupting immune homeostasis in the GI tract. Furthermore, alterations in the microbiota and, specifically, in the virome composition and viral-host interactions have been implicated in perpetuating chronic intestinal inflammation in IBD. By synthesizing current knowledge on viral contributions to immune-mediated GI diseases, this review aims to provide insights into the complex interplay between viral infections, host genetics, and virome dysbiosis, shedding light on novel therapeutic strategies aimed at mitigating the burden of these debilitating conditions on patients' health and quality of life.

An international multicentre study of SwiTching from Intravenous to subcutaneous inflixiMab and vEdolizumab in inflammatory bowel diseases: The TIME study.

BACKGROUND AND AIMS: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. METHODS: This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. RESULTS: Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. CONCLUSION: SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders-A Comprehensive Review.

Eosinophilic Gastrointestinal Disorders (EGIDs) are a group of conditions characterized by abnormal eosinophil accumulation in the gastrointestinal tract. Among these EGIDs, Eosinophilic Esophagitis (EoE) is the most well documented, while less is known about Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EoC). The role of endoscopy in EGIDs is pivotal, with applications in diagnosis, disease monitoring, and therapeutic intervention. In EoE, the endoscopic reference score (EREFS) has been shown to be accurate in raising diagnostic suspicion and effective in monitoring therapeutic responses. Additionally, endoscopic dilation is the first-line treatment for esophageal strictures. For EoG and EoN, while the literature is more limited, common endoscopic findings include erythema, nodules, and ulcerations. Histology remains the gold standard for diagnosing EGIDs, as it quantifies eosinophilic infiltration. In recent years, there have been significant advancements in the histological understanding of EoE, leading to the development of diagnostic scores and the identification of specific microscopic features associated with the disease. However, for EoG, EoN, and EoC, precise eosinophil count thresholds for diagnosis have not yet been established. This review aims to elucidate the role of endoscopy and histology in the diagnosis and management of the three main EGIDs and to analyze their strengths and limitations, their interconnection, and future research directions.

TL1A inhibition for inflammatory bowel disease treatment: From inflammation to fibrosis.

The pivotal role of TL1A in modulating immune pathways crucial for inflammatory bowel disease (IBD) and intestinal fibrosis offers a promising therapeutic target. Phase 2 trials (TUSCANY and ARTEMIS-UC) evaluating an anti-TL1A antibody show progress in expanding IBD therapeutic options. First-in-human data reveal reduced expression of genes associated with extracellular matrix remodeling and fibrosis post-anti-TL1A treatment. Investigational drug TEV-48574, potentially exerting dual antifibrotic and anti-inflammatory effects, is undergoing a phase 2 basket study in both ulcerative colitis (UC) and Crohn disease (CD). Results are eagerly awaited, marking advancements in IBD therapeutics. This critical review comprehensively examines the existing literature, illuminating TL1A and the intricate role of DR3 in IBD, emphasizing the evolving therapeutic landscape and ongoing clinical trials, with potential implications for more effective IBD management.

Microbiota profiling in esophageal diseases: Novel insights into molecular staining and clinical outcomes.

Gut microbiota is recognized nowadays as one of the key players in the development of several gastro-intestinal diseases. The first studies focused mainly on healthy subjects with staining of main bacterial species via culture-based techniques. Subsequently, lots of studies tried to focus on principal esophageal disease enlarged the knowledge on esophageal microbial environment and its role in pathogenesis. Gastro Esophageal Reflux Disease (GERD), the most widespread esophageal condition, seems related to a certain degree of mucosal inflammation, via interleukin (IL) 8 potentially enhanced by bacterial components, lipopolysaccharide (LPS) above all. Gram- bacteria, producing LPS), such as Campylobacter genus, have been found associated with GERD. Barrett esophagus (BE) seems characterized by a Gram- and microaerophils-shaped microbiota. Esophageal cancer (EC) development leads to an overturn in the esophageal environment with the shift from an oral-like microbiome to a prevalently low-abundant and low-diverse Gram--shaped microbiome. Although underinvestigated, also changes in the esophageal microbiome are associated with rare chronic inflammatory or neuropathic disease pathogenesis. The paucity of knowledge about the microbiota-driven mechanisms in esophageal disease pathogenesis is mainly due to the scarce sensitivity of sequencing technology and culture methods applied so far to study commensals in the esophagus. However, the recent advances in molecular techniques, especially with the advent of non-culture-based genomic sequencing tools and the implementation of multi-omics approaches, have revolutionized the microbiome field, with promises of implementing the current knowledge, discovering more mechanisms underneath, and giving insights into the development of novel therapies aimed to re-establish the microbial equilibrium for ameliorating esophageal diseases..

The Inflammatory Bowel Disease Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) framework.

Inflammatory bowel disease (IBD) is a class of chronic disorders whose etiogenesis is still unknown. Despite the high number of IBD-related omics studies, the RNA-sequencing data produced results that are hard to compare because of the experimental variability and different data analysis approaches. We here introduce the IBD Transcriptome and Metatranscriptome Meta-Analysis (TaMMA) framework, a comprehensive survey of publicly available IBD RNA-sequencing datasets. IBD TaMMA is an open-source platform where scientists can explore simultaneously the freely available IBD-associated transcriptomics and microbial profiles thanks to its interactive interface, resulting in a useful tool to the IBD community.